Project Summary (OVERALL) The pathogenic henipaviruses (Nipah and Hendra) are distinguished among the paramyxoviruses by virtue of their uniquely broad tropism and impressive lethality. These viruses can infect animals across 6 orders of mammals, causing an often fatal disease in 11 species including humans. Nipah in Bangladesh is of particular concern, and outbreaks occur annually with near 100% case fatality rates and person-to-person transmission. Currently, there are no vaccines or therapeutics approved for human use. Nipah and Hendra are continuous infectious disease threats both to public health and to economically important livestock throughout South Asia and Australia. The henipaviruses are enveloped RNA viruses and their biology allows them to be synthetically produced, with high potential for misuse as agents of bioterror or biowarfare. There has been significant progress over the last decade in the development of vaccines and postexposure therapies for Nipah and Hendra. Preventive vaccines would have utility for lab workers, first responders or individuals at high risk exposure; but in the case of a biological attack or natural outbreak, a postexposure treatment would be the most practical approach. The henipavirus G and F glycoproteins are the major targets of neutralizing antibodies and the cornerstone of vaccine strategies. All three Research Projects (RP) in the Center focus on developing strategies effective against all pathogenic henipaviruses. RP1 focuses on the soluble Hendra G glycoprotein vaccine, RP2 focuses on human anti-henipavirus monoclonal antibodies, and RP3 focuses on recombinant Cedar virus-based vaccines. A unique aspect of this Center is that it includes both of the most- studied countermeasures that have shown the ability to provide complete pre- and post-exposure protection of nonhuman primates against Nipah/Hendra infection. The level of certain advancements among the RPs is a major strength and advantage of our Center. The primary objective of the Advancement of Vaccines and Therapies for Henipaviruses Center is to perform pivotal studies that will facilitate the development of products used for the prevention and treatment of Nipah and Hendra infections. The cooperation among the three RPs, Administrative Core, human monoclonal antibody Core and Biosafety Level (BSL)-4 Core is built into the Center by design, as all components work together to provide broadly effective countermeasures. Quality system data management will be employed in both the preparation of advanced stage test articles and in the conduct of animal studies. Relevance (OVERALL) Nipah and Hendra, are highly pathogenic viruses and threats to both human and livestock health. They are available in nature, can be synthetically generated and easily produced and disseminated, with the potential for high mortality rates and major public heath impact. There are no countermeasures approved for human use. This Center focuses on the advanced development of the most promising antivirals, including the only strategy shown to offer postexposure protection of nonhuman primates against henipaviruses.